The serological analysis of human cancer has been revolutionized by the introduction of the hybridoma technology (Kohler, G. & Milstein, C. (1975) Nature 256:495-497. Knowledge about the surface antigenic structure of several types of human cancers has advanced rapidly with mouse monoclonal antibodies as serological probes, and application of these reagents to cancer diagnosis and therapy is underway. Production of human monoclonal antibodies, however, has proved more difficult to achieve. Despite much effort by many laboratories around the world, there are relatively few reports of success in the literature. The two approaches that have been explored most vigorously are transformation of B cells by Epstein-Barr virus (EBV) (Steinitz, M., Klein, G., Koskimies, S. & Makel, O. (1977) Nature 269:420-422, Koskimies, S. (1980) Scand. J. Immunol. 11:73-77. and hybridization of B cells with drug-marked mouse or human myeloma or lymphoblastoid cells lines (Olsson, L. & Kaplan, H. S. (1980) Proc. Nat'l. Acad. Sci., U.S.A. 77:5429-5431, Croce, C. M., Lennenbach, A., Hall, W., Steplewski, Z. & Koprowski, H. (1980) Nature 288488-489, Nowinski, R., Berglund, C., Lane, J., Lostrom, M., Bernstein, I., Young, W., Hakomori, S., Hill, L. & Cooney, M. (1980) Science 210:537-539, Schlom, J., Wunderlick, D. & Teramoto, Y. A. (1980) Proc. Nat'l. Acad. Sci., U.S.A. 77:6841-6845, Lane, H. C., Shelhamer, J. H. Mostowski, H. S. & Fauci, A. S. (1982) J. Exp. Med. 155:333-338). Difficulties in establishing stable antibody-secreting clones has been a major problem with EBV transformation, and a low frequency of hybrid clones resulting from fusion of human lymphocytes with human B cell lines has limited progress with this approach to producing human monoclonal antibodies. Although fusion of human lymphocytes with mouse myeloma results in substantial numbers of hybrids secreting human immunoglobulin (Ig) (Nowinski, R., Berglund, C., Lane, J., Lostrom, M., Bernstein, I., Young, W., Hakomori, S., Hill, L. & Cooney, M. (1980) Science 210:537-539. and Schlom, J., Wunderlich, D. & Teramoto, Y. A. (1980) Proc. Nat'l. Acad.. Sci., U.S.A. 77:6841-6845), there is a general feeling that these interspecies hybrids are rather unstable. Nevertheless, several mouse/human hybrids that continued to secrete Ig for extended periods have been isolated (Nowinski, R., Berglund, C., Lane, J., Lostrom, M., Bernstein, I., Young, W., Hakomori, S., Hill, L. & Cooney, M. (1980) Science 210:537-539. and Lane, H. C., Shelhamer, J. H. Mostowski, H. S. & Fauci, A. S. (1982) J. Exp. Med. 155:333-338).
Edwards et al. (Edwards, P. A. W., Smith, C. M., Neville, A. M. & O'Hare, M. J. (1982) Eur. J. Immunol. 12:641-648) have recently described a hyposanthine guanine phosphoribosyl transferase (HGPRT)-deficient human lymphoblastoid line, LICR-LON-HMy2 (LICR-2), that grows vigorously, has been shown to fuse with human lymphocytes and produces hybrids that secrete human Ig distinguishable from the Ig of the parental line (Edwards, P. A. W., Smith, C. M., Neville, A. M. & O'Hare, M. J. (1982) Eur. J. Immunol. 12:641-648, Sikora, K., Alderson, T. Phillips, J. & Watson, J. V. (1982) Lancet 2:11-14). Efforts have been exerted to use this cell line, and two other cell lines, the SKO-007 line of Olsson and Kaplan (Olsson, L. & Kaplan, H. S. (1980) Proc. Nat'l. Acad. Sci., U.S.A. 77:5429-5431. and the mouse myeloma, NS-1 (Kohler, G. & Milstein, C. (1976) Eur. J. Immunol. 6:511-519) to make hybridomas that produce human Ig antibodies.